1. Technical Field
The present invention relates to a method for diagnosing or predicting susceptibility to a psychiatric disorder, especially schizophrenia, bipolar disorder and the like.
2. Art Related
Currently differential diagnosis for psychiatric disorders is largely phenomenological. Diagnosis is based on observation of certain subset of symptoms and the course of disorders. The Diagnostic and Statistical Manual (DSM) of Mental Disorders (the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th edition, 1994) is widely used. Although considerable research efforts have been conducted for developing biological and biochemical assessment to psychiatric disorders, almost none of objective markers has been utilized in their diagnostic criteria.
Schizophrenia is one of the most devastating psychiatric disorders, as defined by DSM-IV, characterized by psychotic symptoms involving disturbances of thought, emotion, and perception.
Schizophrenia occurs worldwide as a common disease such as hypertension and diabetic etc. Although its etiology remains elusive, multiple lines of evidence favor genetic predisposition to schizophrenia. Linkage analyses for schizophrenia have indicated multiple chromosomal loci, suggesting the existence of certain candidate genes as its susceptibility factors. Brain imaging and neuropathological assessments suggest that abnormalities in schizophrenic include aberrant cerebral cortical development that might reflect cytoskeletal disturbances.
In a Scottish family, a balanced chromosome (1;11)(q42.1; q14.3) translocation associates with occurrence of major psychiatric disorders (schizophrenia and mood disorders) with a logarithm of odds score of 7.1. This translocation interrupts the coding sequences of a transcript, named as Disrupted-in Schizophrenia-1 (DISC1), leading to loss of the C-terminal 257 amino acids for DISC1 protein.
It was reported that transient expression of mutant DISC1 protein (mutDISC1), but not wild-type DISC1 protein (wtDISC1) in PC12 cells inhibits neurite outgrowth (PNAS vol. 100, No. 1, 289-294, 2003). It has also been reported that stable transfection of wtDISC1 in PC12 cells enhances neurite extension (Molecular Psychiatry vol. 8, No. 7, 685-694, 2003).
wtDISC1 is expressed mainly in the centrosome, in contrast, mutDISC1 widely distributed in the cytoplasm (PNAS vol. 100, No. 1, 289-294, 2003, Human Molecular Genetics vol. 12, No. 13, 1591-1608, 2003).
Although these prior arts have provided information on subcellular localization of DISC1 and clues for its functions, they have not addressed pathophysiology when wtDISC1 is impaired. Thus, involvement of DISC1 in more general schizophrenia and related mental illnesses, without the unique mutation of DISC1 (mutDISC1) found in the Scottish family, is still unclear.